1. Field of the Invention
This invention relates to novel imidazole derivatives. More particularly, this invention relates to novel imidazole derivatives of the formula: ##STR3## wherein R is a hydrogen atom or an alkyl group, A.sub.1 and A.sub.2, which may be the same or different, each is an alkylene or an alkenylene group, m is 0 or 1, and Z is ##STR4## wherein R.sub.1 and R.sub.2, which may be the same or different, each is a hydrogen atom or an alkyl group, and the terminal carbon atom bonded to the hetero atom of Z may be bonded to A.sub.1 or A.sub.2 or COOR group (in the case of m being 0); and to pharmaceutical compositions containing them.
2. Description of the Prior Art
Up to now, of the compounds having an imidazole skeleton, it has been reported that imidazole, 1-alkylimidazoles, 1-benzylimidazole, 1-(2-isopropylphenyl)imidazole and their analogues possess an inhibitory action for thromboxane synthetase [Prostaglandins, Vol. 13, No. 4, 611- (1977), BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol. 80, No. 1, 236- (1978)]. However, since imidazole and 1-lower alkylimidazoles of these compounds above show only very weak inhibitory effect, these compounds are hardly applicable as practically effective medicines. On the other hand, 1-benzylimidazole, 1-(2-isopropylphenyl)imidazole, 1-higher alkylimidazoles such as 1-nonylimidazole and 1-decylimidazole, and their analogues show a strong inhibitory effect as compared with the imidazole and 1-lower alkylimidazoles, but the inhibitory potency of these compounds is yet far from satisfactory one as therapeutically active agents. In addition, the action of these compounds is not a specific inhibitory action for thromboxane synthetase because of possessing both inhibitory actions for thromboxane synthetase and cyclooxygenase. Furthermore, in the case of 1-(2-isopropylphenyl)imidazole, the preparation of this compound is difficult, so that the problem of industrial application remains still unsettled.
Meanwhile, many compounds which have an imidazole skeleton and which might be considered superficially to be similar to the compounds of this invention from a chemical structural standpoint have been reported, e.g., in J. Chem. Soc., 1670-(1975), Monatsch Chem., Vol. 108, No. 5, 1059- (1977), J. Med. Chem., Vol. 18, No. 8, 833- (1976), J. Amer. Chem. Soc., Vol. 79, 4922- (1957), U.S. Pat. No. 3,541,109, French Pat. No. 7,799M, French Pat. No. 1,486,817, Chemical Abstracts, Vol. 71, 90,645g (1969), ibid., 83, 164,069u (1975), ibid., 88, 36,814z (1978), J. Org. Chem., Vol. 22, 1323- (1975), British Pat. No. 1,148,103, etc. However, all compounds disclosed in the above literature are not reported as to whether or not they exhibit an action for thromboxane synthetase.
Therefore, research for some compounds possessing a much stronger and more specific inhibitory effect on thromboxane synthetase has been long demanded in the medical field.
As a result of extensive research and experimentation carried out for imidazole derivatives, it was found that such demand was satisfied with use of the compounds of the formula (I).
The imidazole derivatives of this invention possess a strong and specific inhibitory effect on thromboxane synthetase and are useful as therapeutically active agents for the treatment of inflammation, hypertension, thrombus, cerebral apoplexy and asthma.